Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease

Abstract

OBJECTIVE Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytes may be a source of CRP in CD and whether inflammatory and bacterial triggers may stimulate its production by adipocytes. DESIGN CRP expression in the mesenteric and subcutaneous fats of patients with CD and the correlation between CRP plasma concentrations and mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory and bacterial challenges on CRP synthesis was tested using an adipocyte cell line. Bacterial translocation to mesenteric fat was studied in experimental models of colitis and ileitis and in patients with CD. RESULTS CRP expression was increased in the mesenteric fat of patients with CD, with mRNA levels being 80 ± 40 (p<0.05) and 140 ± 65 (p=0.04) times higher than in the mesenteric fat of patients with ulcerative colitis and in the subcutaneous fat of the same CD subjects, respectively, and correlated with plasma levels. Escherichia coli (1230 ± 175-fold, p<0.01), lipopolysaccharide (26 ± 0.5-fold, p<0.01), tumour necrosis factor α (15 ± 0.3-fold, p<0.01) and interleukin-6 (10 ± 0.7-fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial translocation to mesenteric fat occurred in 13% and 27% of healthy and CD subjects, respectively, and was increased in experimental colitis and ileitis. Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1 and NOD2. CONCLUSION Mesenteric fat is an important source of CRP in CD. CRP production by mesenteric adipocytes may be triggered by local inflammation and bacterial translocation to mesenteric fat, providing a mechanism whereby mesenteric fat hyperplasia may contribute to inflammatory response in CD.

DOI: 10.1136/gutjnl-2011-300370

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@inproceedings{PeyrinBiroulet2012MesentericFA, title={Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease}, author={L Peyrin-Biroulet and Florent Gonzalez and Laurent Dubuquoy and Christel Rousseaux and Caroline Dubuquoy and C{\'e}cilia Decourcelle and Alain Saudemont and Mickael Tachon and Elodie B{\'e}clin and M Odou and Christel Neut and J -F Colombel and Pierre Desreumaux}, booktitle={Gut}, year={2012} }